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Flashcards in Microbial toxins Deck (11)
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6 mechanisms of action for microbial toxins

1. Toxins that facilitate spread of microbes through tissues
2. Toxins that damage cellular membranes
3. Toxins that stimulate cytokine production
4. Toxins that inhibit protein synthesis
5. Toxins that modify intracellular signaling pathways
6. Toxins that inhibit the release of NT


How do toxins damage cellular membranes?

i. Most kill target cells by forming pores / disrupting membrane integrity
ii. Many are called hemolysins because they damage erythrocytes
iii. If they also damage other cells they are called cytolysins


How do toxins that stimulate cytokine production cause harm?

Streptococcus pyogenes and Staphylococcus aureus produce pyrogenic exotoxins → bind both MHC Class II and to specific V-beta chains on T-cells. → Activates T-cells→ TONS of cytokines → DAMAGE


Why are Toxins that inhibit protein synthesis bad for us? Example

can irreversibly cause death of hosts
i. Diphtheria toxin and Pseudomonas aeruginosa inactivate EF-2


Heat-labile enterotoxins (LTs) of Vibrio cholerae and E. coli

1) increase cAMP 2) Activate α-subunit of stimulatory Gs protein
3) Increased intracellular cAMP causes active Cl- secretion and results in diarrhea


Heat-stable enterotoxin I (ST-I) of E. coli

1) Activates cGMP
2) Increased intracellular cGMP causes secretory diarrhea


Anthrax edema factor (EF) from bacillus anthracis & adenylate cyclase toxin from Bordetella pertussis:

1) Adenylate cyclases that increase cAMP
2) Require activation by calmodulin and calcium - provided by target cells
3) Targets cardiomyocytes and smooth muscle/endothelial cells for lethal effects


Explain the principles for developing novel therapeutic agents based on toxins

Immunotoxins & hormonotoxins - hybrid molecules

○ Lack the receptor-binding domain of the native toxin
○ Use the "A" (active) part of the toxin by coupling it to an Ab that is specific to the cell you want to destroy. --> The toxin can kill specific cells for you now (won’t kill cells without the tumor-specific receptor)


Stage 1 bacterial cell wall synthesis inhibitors

Affects Synthesis and assembly of cell wall subunits occurring in the cytosol


Stage 2 bacterial cell wall synthesis inhibitors

Affects Linear polymerization of subunits occurring at cell membrane

ie: vancomycin


Stage 3 bacterial cell wall synthesis inhibitors

affects Cross-linking of peptidoglycan polymers occurring at the cell wall